Apolipoprotein E modulates establishment of HSV-1 latency and survival in a mouse ocular model.

PURPOSE: To evaluate and compare the neuroinvasiveness and neurovirulence after ocular HSV-1 infection in ApoE knockout (ApoE-/-) and control C57BL/6 (ApoE+/+) mice. METHODS: Age-matched (14 weeks of age) C57BL/6J (ApoE+/+) female mice and female ApoE knockout (ApoE-/-) mice were inoculated by corneal scarification with HSV-1 strain 17Syn+. Analysis of HSV-1 replication in the mouse cornea was assessed through infectious virus assays of ocular (tear film) swabs at 1 to 5 days postinoculation (PI), slit-lamp examination (SLE) of corneas at PI days 1 to 7, and survival of infected mice. The contribution of apoE to the efficient establishment of latency was measured by real-time PCR quantitation of the latent viral genome in the trigeminal ganglia (TG) of infected mice. RESULTS: These studies showed that HSV-1 strain 17Syn+ replicates efficiently in the eyes, regardless of the host ApoE genotype. Neither the scoring of corneal pathology via SLE nor the infectious virus assay of the tear film resulted in any statistical differences between ApoE knockout (-/-) mice or the C57BL/6 (ApoE+/+) mice. In mice latently infected with HSV-1, our real-time PCR data showed significantly lower viral copy numbers of HSV-1 DNA in ApoE knockout (ApoE-/-) mice compared with C57BL/6 (ApoE+/+) mice. C57BL/6 (ApoE+/+) mice are more susceptible to the neurovirulence of HSV-1 strain 17Syn+ than female ApoE knockout (-/-) mice, as demonstrated by the fact that 50% (7/14) of the female C57BL/6 (ApoE+/+) mice inoculated with 17Syn+ died, as opposed to none (0/14) of the age- and sex-matched ApoE knockout mice. CONCLUSIONS: These data indicate that age (14 weeks) and sex-matched (female) wild mice with an ApoE null background (ApoE-/-) are more resistant and less efficient in the establishment of latency compared with ApoE+/+ mice in the C57BL/6 background.